The objective of the proposed research is to gain a better understanding of the mechanisms governing the stimulation and control of human lymphocte DNA replication and cell division. Experiments will utilize lymphocytes from normal donors and from patients with abnormalities in lymphocyte function, due to either malignancy or an immunological disorder. Detailed cell cycle kinetic studies of in vitro stimulated lymphocyte cultures will be performed, taking into account recruitment of cells into the cycling population, inhibitory factors and cell death. Cyclic AMP metabolism will be studied in normal and abnormal lymphocytes, in order to better understand its role in the regulation of lympocyte proliferation. In addition, we will attempt to characterize and determine the explanation for the presence of actively cycling lymphocytes in the peripheral blood of certain patients, particularly those with Hodgkin's disease.